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Biomedical subjects

J Rodriguez

Publications and source records attributed to J Rodriguez.

At least 73 records · Page 4Linked to original sources

Absolute structures of new briarane diterpenoids from junceella fragilis

Four new diterpenoids with the briarane skeleton, (-)-4-deacetyljunceellolide D (2), (+)-11alpha, 20alpha-epoxyjunceellolide D (3), (-)-11alpha, 20alpha-epoxy-4-deacetyljunceellolide D (4), and (-)-11alpha, 20alpha-epoxy-4-deacetoxyjunceellolide D (5), (+)-junceellolide A (6) [the antipodal derivative of the known (-)-junceellolide A], along with three known briaranes, (-)-junceellolide D (1), (-)-junceellin (7), and (-)-praelolide (8), were isolated from the Indonesian gorgonian Junceella fragilis. The structures of the new compounds were established on the basis of extensive NMR studies and by comparison with the spectral data from other briarane compounds. The absolute configurations for four of the compounds were determined by the modified Mosher method and by unambiguous chemical interconversions.

Journal Article↗

Phase II study of paclitaxel in combination with mitoxantrone and ifosfamide/mesna for patients with relapsed or refractory non-Hodgkin's lymphoma after failure to cytarabine/cisplatin combination.

PURPOSE: Evaluate response, duration of response, and toxicity of paclitaxel in combination with other drugs known to be effective in non-Hodgkin's lymphoma (NHL). METHODS: Thirty-eight patients with relapsed/refractory NHL who had been exposed to doxorubicin as well as the cytarabine-cisplatin combinations received Mesna 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour; ifosfamide 1.33 gm/M2/D daily days 1, 2, 3 i.v. over 1 hour (same bag); Novantrone 8 mg/M2/D i.v. day 1; and Taxol 27.5 mg/M2/D daily days 1, 2, 3, 4 by continuous 24-hour intravenous infusion. Premedication for Taxol included dexamethasone, diphenhydramine, and cimetidine on day 1. RESULTS: Of 35 evaluable patients, 9 (26%) achieved a complete response and 7 (20%) a partial response for a total response rate of 46%. The median failure-free and overall survival times were 2 and 10 months, respectively. Major toxicity was hematologic with a median absolute neutrophil nadir of 196/mm3. Only 10% of the cycles were associated with a grade 3-4 infection. CONCLUSION: MINT is an active and safe regimen for relapsed/refractory NHL that have failed both an Adriamycin-containing regimen and a cytarabine/cisplatin-containing regimen.

Adult↗

Allogeneic hematopoietic transplantation for mantle-cell lymphoma: molecular remissions and evidence of graft-versus-malignancy.

BACKGROUND: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation. PATIENTS AND METHODS: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. RESULTS: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) for bcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%-83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%-100%) compared with 44% (95% CI: 1%-88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). CONCLUSIONS: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.

Adult↗

Phylogenetic differentiation of two closely related Nitrosomonas spp. That inhabit different sediment environments in an oligotrophic freshwater lake.

The population of ammonia-oxidizing bacteria in a temperate oligotrophic freshwater lake was analyzed by recovering 16S ribosomal DNA (rDNA) from lakewater and sediment samples taken throughout a seasonal cycle. Nitrosospira and Nitrosomonas 16S rRNA genes were amplified in a nested PCR, and the identity of the products was confirmed by oligonucleotide hybridization. Nitrosospira DNA was readily identified in all samples, and nitrosomonad DNA of the Nitrosomonas europaea-Nitrosomonas eutropha lineage was also directly detected, but during the summer months only. Phylogenetic delineation with partial (345 bp) 16S rRNA gene sequences of clones obtained from sediments confirmed the fidelity of the amplified nitrosomonad DNA and identified two sequence clusters closely related to either N. europaea or N. eutropha that were equated with the littoral and profundal sediment sites, respectively. Determination of 701-bp sequences for 16S rDNA clones representing each cluster confirmed this delineation. A PCR-restriction fragment length polymorphism (RFLP) system was developed that enabled identification of clones containing N. europaea and N. eutropha 16S rDNA sequences, including subclasses therein. It proved possible to analyze 16S rDNA amplified directly from sediment samples to determine the relative abundance of each species compared with that of the other. N. europaea and N. eutropha are very closely related, and direct evidence for their presence in lake systems is limited. The correlation of each species with a distinct spatial location in sediment is an unusual example of niche adaptation by two genotypically similar bacteria. Their occurrence and relative distribution can now be routinely monitored in relation to environmental variation by the application of PCR-RFLP analysis.

Cloning, Molecular↗

Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells.

32D cells, a murine myeloid cell line, rapidly undergo apoptosis upon withdrawal of interleukin-3 (IL-3) supplement in culture. We found that 32D cells, if infected by several species of human mycoplasmas that rapidly activated NF-kappaB, would live and continue to grow in IL-3-depleted culture. Mycoplasma-infected cells showed no evidence of autocrine production of IL-3. Pyrrolidine dithiocarbamate (PDTC) blocked activation of NF-kappaB and led to prominent cell death. Heat-killed mycoplasmas or mycoplasmal membrane preparations alone could support continued growth of 32D cells in culture without IL-3 supplement for a substantial period of time. However, upon removal of heat-inactivated mycoplasmas, 32D cells quickly became apoptotic. In comparison, live Mycoplasma fermentans or M. penetrans infection for 4 to 5 weeks induced malignant transformation of 32D cells. Transformed 32D cells grew autonomously and no longer required support of growth-stimulating factors including IL-3 and mycoplasmas. The transformed 32D cells quickly formed tumors when injected into nude mice. Karyotyping showed that development of chromosomal changes and trisomy 19 was often associated with malignant transformation and tumorigenicity of 32D cells. Mycoplasmal infections apparently affected the fidelity of genomic transmission in cell division as well as checkpoints coordinating the progression of cell cycle events.

Animals↗

Chaplains' communications with Latino patients: case studies on non-verbal communication.

Introduces non-Latino chaplains to aspects of non-verbal communications dynamics one may encounter with some Latino patients. Illustrates through vignettes issues of non-verbal communications. Compares and contrasts classical understandings of professional etiquette to Latino views. Provides specific "insights" into the communication styles among some Latinos. Includes a list of non-verbal messages and their generic interpretations.

Clergy↗

Oncogene-dependent apoptosis is mediated by caspase-9.

Understanding how oncogenic transformation sensitizes cells to apoptosis may provide a strategy to kill tumor cells selectively. We previously developed a cell-free system that recapitulates oncogene dependent apoptosis as reflected by activation of caspases, the core of the apoptotic machinery. Here, we show that this activation requires a previously identified apoptosis-promoting complex consisting of caspase-9, APAF-1, and cytochrome c. As predicted by the in vitro system, preventing caspase-9 activation blocked drug-induced apoptosis in cells sensitized by E1A, an adenoviral oncogene. Oncogenes, such as E1A, appear to facilitate caspase-9 activation by several mechanisms, including the control of cytochrome c release from the mitochondria.

Adenovirus E1A Proteins↗

Iron-binding catechols oxidating lignin and chlorolignin.

Iron-chelating low-molecular-weight compounds or catecholate siderophores have been suggested to be involved in wood biodegradation. To help in understanding the mechanism involved in the enzyme-like activity of catecholate siderophores, the oxidative properties of 2,3-dihydroxybenzoic acid (DHBA) and 3, 4-dihydroxyphenylacetic acid (DHPAA) chelated with iron were studied. The pH and catechol/Fe(III) ratios were optimized for o-dianisidine oxidation, obtaining a maximum at pH 7.0, in the absence of buffer, and a catechol/Fe(III) ratio of 1:2 to DHBA and 1:1 to DHPAA was found. Under these conditions, the catechols were able to reduce Fe(III) to Fe(II) acting like siderophore models. The Fe(III) complex of DHBA and of DHPAA degraded dioxane-lignin in 60% after 2 h and 85% after 24 h, respectively. DHBA/Fe(III) oxidized the bleaching effluent (E1) in 80% in 5 min under the studied conditions.

3,4-Dihydroxyphenylacetic Acid↗

Hydroxamate iron complex with phenoloxidase activity acting on lignin and chlorolignins.

The properties of a siderophore model, acetohydroxamic acid (AHA), of desferral were studied. The pH, ionic strength, and AHA/Fe(III) ratios for o-dianisidine oxidation were optimized. Phenoloxidase activity of hydroxamates/Fe(III) acting on o-dianisidine at pH 7.0 and pH 3.0 was observed. Under these conditions, AHA was able to reduce Fe(III) to Fe(II) followed by ferrozine complexation. AHA/Fe(III) complex degraded lignin and chlorolignins from kraft effluent E1 65% and 85%, respectively, after 24 h.

Biodegradation, Environmental↗

Mucoepidermoid carcinoma ex pleomorphic adenoma: nonspecific preoperative cytologic findings in six cases.

BACKGROUND: In contrast to most major salivary gland malignancies, mucoepidermoid carcinoma has been rarely documented and tentatively accepted as carcinoma ex pleomorphic adenoma. The authors present the cytologic and clinical findings for six examples of these rare tumors. METHODS: The six examples were identified during an extensive review of the authors' salivary gland files, and all were high grade mucoepidermoid carcinomas on histologic evaluation. RESULTS: Overall, mucoepidermoid carcinomas cytologically presented as non-specific high grade malignancies and consisted of highly malignant cells, in clusters or isolated, that were rarely associated with intracellular and extracellular mucin. In only two cases, a background of cellular and stromal elements consistent with pleomorphic adenoma was identified. CONCLUSIONS: Although it is nearly impossible cytologically to distinguish these lesions from other high grade primary or metastatic carcinomas (such as poorly differentiated squamous cell carcinomas, adenosquamous carcinomas, and salivary duct carcinomas), this limitation is not dramatic, as a cytologic diagnosis of high grade malignancy per se allows for proper preoperative patient management.

Adenoma, Pleomorphic↗

The corticostriatal system mediates the "paradoxical" contraversive rotation but not the striatal hyperexpression of Fos induced by amphetamine early after 6-hydroxydopamine lesion of the nigrostriatal pathway.

In rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway, amphetamine produces ipsiversive rotational behavior and activation of Fos in the intact striatum, but practically no activation of Fos in the denervated striatum. However, a seemingly paradoxical contraversive rotation, accompanied by intense striatal Fos activation in the lesioned striatum, has been observed during the first few days postlesion. In the present work, behavioral tests and immunohistochemistry for Fos protein and tyrosine hydroxylase (TH) were combined to study striatal changes 36 h after 6-OHDA lesion and particularly the possible involvement of glutamatergic corticostriatal afferents. Injection of amphetamine (0.5 mg/kg or 5 mg/kg) induced contraversive rotation and strong and evenly distributed Fos expression in the lesioned striatum; in the contralateral striatum, however, Fos density was lower than in nonlesioned rats. Pretreatment with the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (either 0.5 mg/kg or 5 mg/kg) did not significantly affect the hyperexpression of Fos in the lesioned striatum, but suppressed the contraversive rotation. Similarly, rats that were subjected to corticostriatal deafferentation (confirmed by sensory neglect tests) and 6-OHDA lesion (1 week or 3 weeks later) showed no significant reduction in the striatal Fos hyperexpression induced by amphetamine (0.5 mg/kg or 5 mg/kg) and no significant rotational asymmetry. In conclusion, the present results indicate that glutamatergic corticostriatal afferents are essential for the contraversive rotational behavior but not the striatal hyperexpression of Fos observed in response to amphetamine early after 6-OHDA lesion, and suggest that intense dopaminergic stimulation of striatal neurons is sufficient for induction of Fos, but that concurrent glutamatergic stimulation is necessary for the motor response.

Afferent Pathways↗

How, when, and why bile duct injury occurs. A comparison between open and laparoscopic cholecystectomy.

BACKGROUND: Bile duct injury (BDI) is a severe complication of laparoscopic cholecystectomy (LC). There is general agreement about the increase of this complication after LC vs open cholecystectomy (OC), but comparative studies are scarce. The aim of this paper has been to compare the incidence and clinical features of BDI after LC vs open procedures. MATERIALS AND METHODS: 3,051 OC, performed from June 1977 to December 1988 were retrospectively analyzed and compared with 1,630 LCs performed from June 91 to August 96, for which data were prospectively recorded. Age, sex, type of BDI, performance of intraoperative cholangiography (IOC), underlying biliary pathology, morbidity, mortality, and late morbidity were all analyzed. RESULTS: BDI incidence was higher in group II (LC) (N: 16, 0.95%) than in group I, (OC, N: 19. 0.6%). BDI incidence was also higher in the group of patients in which it was necessary to convert to an open procedure (3/109, 2.7%, p < 0.05). BDIs were more frequently diagnosed intraoperatively in group I (OC, 18/19) than in group II (LC, 12/16). In both groups, BDI was more prevalent in cases operated by staff surgeons than residents, mainly in complicated gallbladder patients, with a bile duct of less than 7-mm diameter. Morbidity, postoperative stay, mortality, and late morbidity were similar after a BDI in both types of approach. CONCLUSIONS: (1) BDI increases with LC. (2) BDI after LC carries a similar postoperative morbidity and mortality to those after OC. (3) Incidence of BDI in converted cases increases significantly and this constitutes a high-risk group.

Aged↗

Occupational asthma caused by exposure to asparagus: detection of allergens by immunoblotting.

BACKGROUND: Vegetables of the Liliaceae family, such as garlic or onion, have been reported to cause occupational asthma. However, there are few data on adverse reactions to asparagus. We evaluated the role of asparagus as a cause of asthma in a patient with respiratory symptoms occurring at work (horticulture) and studied relevant allergens. METHODS: A 28-year-old man complained of rhinoconjunctivitis and asthma when harvesting asparagus at work. Eating cooked asparagus did not provoke symptoms. A positive skin test reaction was observed with raw asparagus, Alternaria alternata, and grass-pollen extracts. The methacholine test demonstrated mild bronchial hyperresponsiveness. The patient had an immediate asthmatic response after challenge with raw asparagus extract. Bronchial provocation tests with boiled asparagus, A. alternata, and control extracts were negative. Two unexposed subjects with seasonal allergic asthma did not react to the raw asparagus extract. RESULTS: The double-blind, placebo-controlled food challenge with raw asparagus was negative. Serum asparagus-specific IgE was 13.9 kU(A)/l. By SDS-PAGE immunoblot, at least six IgE-binding components, ranging from 22 to 73 kDa, were detected only in raw asparagus. CONCLUSIONS: We report a case of occupational asthma caused by asparagus inhalation, confirmed by specific bronchoprovocation. Immunoblot analysis showed that asparagus allergens are very labile and quite sensitive to heat denaturation.

Adult↗

Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stages.

A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines.

Amides↗

Modeling of facet articulation as a nonlinear moving contact problem: sensitivity study on lumbar facet response.

A finite element (FE) based scheme for modeling facet articulation in a spinal motion segment is proposed. The algorithm presented models the facet articulation as a nonlinear progressive contact problem. This algorithm is used to perform a nonlinear FE analysis of a complete L3-L4 motion segment. The role of facets in load transmission through a motion segment and its sensitivity to facet geometric parameters (i.e., spatial orientation of the facets and the gap between the facet articular surfaces) on this load transmission are studied. Compression, flexion, extension, and torsion loads are used in this study. The effect of facetectomy on gross segment response and disk fiber strains is studied by comparing the response of FE models of motion segment with and without facets. Large facet loads are obtained when the motion segment is subjected to torsional and large extension rotations, whereas minimal facet loads are observed under compression and flexion loading. Removal of facets reduces the segment stiffness considerably in torsion and results in higher strain levels in disk fibers. The facet load transmission is sensitive to facet geometric parameters, i.e., spatial orientation and initial facet joint gap. The facet loads increase uniformly with decrease in initial gap between the facet articular surfaces under compression, extension, and torsional loads. The sensitivity to spatial orientation angles of the facet is, however, found to vary with the type of loading. This sensitivity may account for the wide variation in the facet response reported in literature.

Biomechanical Phenomena↗

A leucine zipper-like domain is essential for dimerization and encapsidation of bluetongue virus nucleocapsid protein VP4.

The bluetongue virus (BTV) minor protein VP4, with molecular mass of 76 kDa, is one of the seven structural proteins and is located within the inner capsid of the virion. The protein has a putative leucine zipper near the carboxy terminus of the protein. In this study, we have investigated the functional activity of this putative leucine zipper by a number of approaches. The putative leucine zipper region (amino acids [aa] 523 to 551) was expressed initially as a fusion protein by using the pMAL vector of Escherichia coli, which expresses a maltose binding monomeric protein. The expressed fusion protein was purified by affinity chromatography, and its size was determined by gel filtration chromatography. Proteins of two sizes, 51 and 110 kDa, were recovered, one equivalent to the monomeric form and the other equivalent to the dimeric form of the fusion protein. To prove that the VP4-derived sequence was responsible for dimerization of this protein, a mutated fusion protein was created in which a VP4 leucine residue (at aa 537) within the zipper was replaced by a proline residue. Analyses of the mutated protein demonstrated that the single mutation indeed prevented dimerisation of the protein. The dimeric nature of VP4 was further confirmed by using purified full-length BTV-10 VP4 recovered from recombinant baculovirus-expressing BTV-10 VP4-infected insect cells. Using chemical cross-linking and gel filtration chromatography, we documented that the native VP4 indeed exists as a dimer in solution. Subsequently, Leu537 was replaced by either a proline or an alanine residue and the full-length mutated VP4 was expressed in the baculovirus system. By sucrose density gradient centrifugation and gel filtration chromatography, these mutant forms of VP4 were shown to lack the ability to form dimers. The biological significance of the dimeric forms of VP4 was examined by using a functional assay system, in which the encapsidation activity of VP4 into core-like particles (CLPs) was studied (H. LeBlois, T. French, P. P. C. Mertens, J. N. Burroughs, and P. Roy, Virology 189:757-761, 1992). We demonstrated conclusively that dimerization of VP4 was essential for encapsidation by CLPs.

ATP-Binding Cassette Transporters↗

Health service use by African Americans and Caucasians with asthma in a managed care setting.

Managed care plan members provide a population for analysis that minimizes the financial barriers to routine medical care that have been linked to high rates of asthma-related hospitalization, emergency care, and mortality among urban African Americans. We examined patterns of asthma care among 464 African American (AA) and 1,609 Caucasian (C) asthma patients, age 15 to 45 yr, in a southeast Michigan managed care system during 1993. Compared with C, AA had fewer visits to asthma specialists (0.32 versus 0.50 visits/yr, p = 0.002), and filled fewer prescriptions for inhaled steroids (1.44 versus 1.74 Rx/yr, p = 0.038), while being more likely to visit the emergency department with asthma (0.71 versus 0.28 visits/yr, p < 0. 001), to be hospitalized with asthma (0.08 versus 0.03 admissions/yr, p = 0.002), or to have filled prescriptions for oral steroids (0.91 versus 0.59 Rx/yr, p < 0.001). AA were equally likely to have visited a primary care physician for asthma (0.95 versus 0.93 visits/yr, p = 0.81). Similar physician visit profiles and discrepancies in the use of oral steroids persisted when analyzing exclusively low socioeconomic status subgroups. These results suggest that ethnic differences in patterns of asthma-related health care persist within managed care settings and are only partially due to financial barriers.

Adult↗